Maria Roncarolo

Maria Grazia Roncarolo, MD,Professor, Departments of Pediatrics and Medicine, Stanford University School of Medicine

Research Description: A main focus of Dr. Roncarolo’s research has been investigating the mechanisms underlying the pathology of genetic and acquired auto-immune diseases such as Wiskott Aldrich Syndrome (WAS), the IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy X-linked), inflammatory bowel diseases, celiac disease and type 1 diabetes. She discovered that patients with WASP deficiency have a defect in the immunological synapse and an impaired differentiation of CD25+FOXP3+ T regulatory cells. She led the studies on IPEX patients showing defective regulatory and effector functions in patients with different FOXP3 mutations. She demonstrated that treatment with rapamycin and IL-10 restores tolerance in preclinical models of type 1 diabetes and pancreatic islet transplantation by inducing expansion of CD25+FOXP3+ regulatory cells in the tissue and promoting differentiation of T regulatory type 1 (Tr1) cells in the spleen. She established a preclinical in vivo gene therapy protocol using hepatocyte lentiviral vector targeted deliver of insulin peptides, to protect and reverse type 1 diabetes. She showed that cell therapy with polyclonal or antigen specific Tr1 cells prevents pancreatic islet rejection and her current focus is on studies to achieve long-term normoglycemia and immunological tolerance in type 1 diabetes.